BACKGROUND: Chlamydia pneumoniae has been associated with asthma. It has also been suggested that C pneumoniae infection may lead to lung remodeling in a subset of asthmatic patients. Seroreactivity against Chlamydia trachomatis heat shock protein 60 (hsp60), a highly conserved, immunoreactive chaperone protein, is associated with immunopathologic abnormalities, leading to blinding trachoma and tubal infertility. This suggests that the host response to infection may affect chronic inflammatory damage to the eye and the fallopian tubes. The pathogenesis of C trachomatis disease associations is thought to include molecular mimicry (autoimmunity), direct activation of the innate immune response via the CD14/toll-like receptor 4 complex, or both. OBJECTIVE: To study whether airflow limitation in asthma in C pneumoniae-exposed individuals is associated with a specific antibody response to the C pneumoniae hsp60 molecule and not with a genus-specific response to the hsp60 molecule. METHODS: In a case-control study, we evaluated 138 C pneumoniae-exposed primary care patients (86 adult asthmatic cases and 52 nonasthmatic controls) for seroreactivity against a C pneumoniae-specific hsp60 fragment and against the C trachomatis hsp60 molecule. We analyzed associations with asthma and irreversible lung remodeling as measured by means of postbronchodilator forced expiratory volume in 1 second. RESULTS: Twenty-seven percent of asthmatic patients were C pneumoniae hsp60 seropositive vs 8% of controls (P < .01). Controlling for age, sex, and smoking, C pneumoniae hsp60 seropositivity was associated with lower postbronchodilator forced expiratory volume in 1 second in asthmatic patients (P < .05). No comparable associations were present for C trachomatis hsp60. CONCLUSIONS: In individuals with evidence of previous exposure to C pneumoniae infection, a host antibody response against a C pneumoniae hsp60 fragment but not against C trachomatis hsp60 was associated with airflow limitation in adults with asthma.